Abstract

Endoplasmic reticulum (ER) stress activation disturbs bone homeostasis and plays an important role in osteolytic bone diseases development. Cordycepin (3'-deoxyadenosine), a natural structural analog of adenosine, possess multiple pharmacological activities and exerts osteoprotective effect. Genistein can be used as protectors or synergists of adenosine drugs. The aim of the present study was to investigate whether the combination of cordycepin (Cor) and genistein (Gen) regulates proliferation, migration and differentiation of preosteoblast MC3T3-E1 cells in a tunicamycin (TM)-induced acute ER stress model. Cell viability were assessed using cell counting kit-8 (CCK-8) assay and osteoblast migration were evaluated by transwell chamber assay. The differentiation was assessed by alkaline phosphatase (ALP) staining assay. qRT-PCR assay was performed to confirm the establishment of ER stress model and to measure the mRNA level of key molecules involved in osteogenic differentiation. Exposure to the combination of 10μM cordycepin and 10μM genistein had no cytotoxicity in MC3T3-E1 cells, but increased the number of proliferative cells after pretreatment with 2 μg/ml TM. Analogously, ER stress-induced suppression on MC3T3-E1 cells migration was restored to control levels by the administration of cordycepin and genistein combination. Cordycepin and genistein combination significantly up-regulated ALP activity of MC3T3-E1 cells in TM-induced ER stress model. The qRT-PCR data demonstrated that the combined treatment effectively accelerated osteogenic differentiation by enhancing the mRNA level of differentiation markers including collagen type I, ALP, BSP and OPN. These results reveal that the co-administration of cordycepin and genistein exerts synergistic osteoprotective effects and has the potential to serve as a host risk reduction strategy for osteolytic bone diseases associated with ER stress activation.

Keywords: Cordycepin; Genistein; Osteoblast; Endoplasmic Reticulum Stress

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Citation

Citation: Xiting Li., et al. “Synergistic Effects of Cordycepin and Genistein on Preosteoblast MC3T3-E1 Cells with Endoplasmic Reticulum Stress".Acta Scientific Dental Sciences 4.7 (2020): 133-140.

Copyright

Copyright: © 2020 Xiting Li., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.